scholarly journals Age-related alteration of vitamin D metabolism in response to low-phosphate diet in rats

2005 ◽  
Vol 93 (3) ◽  
pp. 299-307 ◽  
Author(s):  
Tsui-Shan Chau ◽  
Wan-Ping Lai ◽  
Pik-Yuen Cheung ◽  
Murray J. Favus ◽  
Man-Sau Wong
Keyword(s):  
Vitamin D ◽  
Mrna Expression ◽  
Age Groups ◽  
Metabolic Clearance ◽  
Adult Rats ◽  
Vitamin D Metabolism ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
Age Related ◽  
25 Hydroxyvitamin D

The responses of renal vitamin D metabolism to its major stimuli alter with age. Previous studies showed that the increase in circulating 1,25-dihydroxyvitamin D (1,25(OH)2D3) as well as renal 25-hydroxyvitamin D3 1-α hydroxylase (1-OHase) activity in response to dietary Ca or P restriction reduced with age in rats. We hypothesized that the mechanism involved in increasing circulating 1,25(OH)2D3 in response to mineral deficiency alters with age. In the present study, we tested the hypothesis by studying the expression of genes involved in renal vitamin D metabolism (renal 1-OHase, 25-hydroxyvitamin D 24-hydroxylase (24-OHase) and vitamin D receptor (VDR)) in young (1-month-old) and adult (6-month-old) rats in response to low-phosphate diet (LPD). As expected, serum 1,25(OH)2D3 increased in both young and adult rats upon LPD treatment and the increase was much higher in younger rats. In young rats, LPD treatment decreased renal 24-OHase (days 1–7, P<0·01) and increased renal 1-OHase mRNA expression (days 1–5, P<0·01). LPD treatment failed to increase renal 1-OHase but did suppress 24-OHase mRNA expression (P<0·01) within 7 d of LPD treatment in adult rats. Renal expression of VDR mRNA decreased with age (P<0·001) and was suppressed by LPD treatment in both age groups (P<0·05) Feeding of adult rats with 10 d of LPD increased 1-OHase (P<0·05) and suppressed 24-OHase (P<0·001) as well as VDR (P<0·05) mRNA expression. These results indicate that the increase in serum 1,25(OH)2D3 level in adult rats during short-term LPD treatment is likely to be mediated by a decrease in metabolic clearance via the down-regulation of both renal 24-OHase and VDR expression. The induction of renal 1-OHase mRNA expression in adult rats requires longer duration of LPD treatment than in younger rats.

scholarly journals Age-Related Changes in the 25-Hydroxyvitamin D Versus Parathyroid Hormone Relationship Suggest a Different Reason Why Older Adults Require More Vitamin D

2003 ◽  
Vol 88 (1) ◽  
pp. 185-191 ◽  
Author(s):  
Reinhold Vieth ◽  
Yasmin Ladak ◽  
Paul G. Walfish
Keyword(s):  
Older Adults ◽  
Vitamin D ◽  
Secondary Hyperparathyroidism ◽  
Age Groups ◽  
The Elderly ◽  
Age Group ◽  
Hydroxyvitamin D ◽  
Age Related ◽  
25 Hydroxyvitamin D ◽  
The Relationship

Vitamin D requirements are thought to vary with age, but there is little comparative evidence for this. One goal in establishing a vitamin D requirement is to avoid secondary hyperparathyroidism. We studied 1741 euthyroid, thyroid clinic outpatients without evidence of calcium abnormalities, ranging in age from 19 to 97 yr, whose serum and urine had been analyzed for calcium, vitamin D, and parathyroid status. We found no effect of age on the 25-hydroxyvitamin D [25(OH)D] concentration associated with specific vitamin D intakes, and there was no relationship between 25(OH)D and 1,25hydroxyvitamin D [1,25(OH)2D]. In every age group, serum 1,25(OH)2D declined with increasing creatinine (P &lt; 0.001). What changed with age included creatinine, which correlated with 25(OH)D (r = 0.146, P &lt; 0.001) only in the youngest age group (19–50 yr) but not in the older age groups (P &gt; 0.1). Creatinine did not correlate with PTH in the youngest age group, but the relationship became significant as age increased (e.g. for the elderly, r = 0.365, P &lt; 0.001). Linear regression of log PTH vs. log 25(OH)D agreed with the natural shape of the relationship observed with scatterplot smoothing, and this showed no plateau in PTH as 25(OH)D increased. We compared PTH concentrations among age groups, based on 20 nmol/liter increments in 25(OH)D. Mean PTH in adults older than 70 yr was consistently higher than in adults younger than 50 yr (P &lt; 0.05 by ANOVA and Dunnett’s t test). PTH levels of the elderly who had 25(OH)D concentrations greater than 100 nmol/liter matched PTH of younger adults having 25(OH)D concentrations near 70 nmol/liter. This study shows that all age groups exhibit a high prevalence of 25(OH)D insufficiency and secondary hyperparathyroidism. Older adults are just as efficient in maintaining 25(OH)D, but they need more vitamin D to produce the higher 25(OH)D concentrations required to overcome the hyperparathyroidism associated with their diminishing renal function.

scholarly journals Regulation of vitamin D-1alpha-hydroxylase and -24-hydroxylase expression by dexamethasone in mouse kidney

2000 ◽  
Vol 164 (3) ◽  
pp. 339-348 ◽  
Author(s):  
N Akeno ◽  
A Matsunuma ◽  
T Maeda ◽  
T Kawane ◽  
N Horiuchi
Keyword(s):  
Vitamin D ◽  
Enzyme Activity ◽  
Mrna Expression ◽  
Direct Action ◽  
Plasma Concentrations ◽  
Mrna Abundance ◽  
Subcutaneous Injections ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
25 Hydroxyvitamin D

We investigated the effects of dexamethasone on vitamin D-1alpha-hydroxylase and -24-hydroxylase expression and on vitamin D receptor (VDR) content in the kidneys of mice fed either a normal (NCD) diet or a calcium- and vitamin D-deficient (LCD) diet for 2 weeks. For the last 5 days mice received either vehicle or dexamethasone (2 mg/kg per day s.c.). Dexamethasone significantly increased plasma calcium concentrations without changing plasma concentrations of 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) in both NCD and LCD groups. Northern blot and enzyme activity analyses in NCD mice revealed that dexamethasone increased renal VDR mRNA expression modestly and greatly increased 24-hydroxylase mRNA abundance and enzyme activity, but did not affect 1alpha-hydroxylase mRNA abundance and enzyme activity. In mice fed an LCD diet, dexamethasone increased renal VDR mRNA expression 1.5-fold, decreased 1alpha-hydroxylase mRNA abundance (52%) and activity (34%), and markedly increased 24-hydroxylase mRNA abundance (16-fold) and enzyme activity (9-fold). Dexamethasone treatment did not alter functional VDR number (B(max) 125-141 fmol/mg protein) or ligand affinity (K(d) 0.13-0.10 nM) in LCD mice. Subcutaneous injections of 1,25(OH)(2)D(3) (0.24 nmol/kg per day for 5 days) into NCD mice strongly increased renal 24-hydroxylase mRNA abundance and enzyme activity, while there was no effect of dexamethasone on renal 24-hydroxylase expression in these mice. This may be due to overwhelming induction of 24-hydroxylase by 1,25(OH)(2)D(3). These findings suggest that glucocorticoid-induced osteoporosis is caused by direct action of the steroids on bone, and the regulatory effect of glucocorticoids on renal 25-hydroxyvitamin D(3) metabolism may be less implicated in the initiation and progression of the disease.

Effect of age on renal responsiveness to parathyroid hormone and calcitonin in rats

1987 ◽  
Vol 114 (2) ◽  
pp. 173-178 ◽  
Author(s):  
H. J. Armbrecht ◽  
N. Wongsurawat ◽  
R. E. Paschal
Keyword(s):  
Parathyroid Hormone ◽  
Age Groups ◽  
Phosphate Transport ◽  
Serum Concentrations ◽  
Adult Rats ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
Age Related ◽  
Old Adult

ABSTRACT The purpose of these studies was to determine whether the responsiveness of the kidney to parathyroid hormone (PTH) and calcitonin changed with age. Experiments were performed in young (3 months old), adult (12–14 months old) and old (22–24 months old) male Fischer 344 rats fed normal diets and thyroparathyroidectomized. Parathyroid hormone was administered i.p. at 24, 12 and 2 h before death and calcitonin was given i.p. at 12 and 2 h before death. Parathyroid hormone significantly increased the conversion of 25-hydroxyvitamin D3 to 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) by renal slices from young but not adult or old animals. A similar age-related decline in the capacity of PTH to raise serum 1,25-dihydroxyvitamin D (1,25-(OH)2D) levels was also seen. Parathyroid hormone significantly decreased tubular reabsorption of phosphorus, increased concentrations of urinary cyclic AMP (cAMP) and increased serum concentrations of calcium in all age groups. In contrast, calcitonin significantly increased 1,25-(OH)2D3 production by renal slices from both young and adult animals. Calcitonin decreased serum concentrations of calcium in young but not in adult rats. These results suggest that there are maturational changes in the PTH- and cAMP-dependent pathways in the kidney but not in the calcitonin- and cAMP-independent pathways. The changes in the PTH- and cAMP-dependent pathways affect the stimulation of 1,25-(OH)2D production but not the inhibition of phosphate transport. J. Endocr. (1987) 114, 173–178

Vitamin D and Calcitonin Treatment in Patients with Femoral Neck Fracture: A Prospective Controlled Clinical Study

1989 ◽  
Vol 17 (3) ◽  
pp. 226-242 ◽  
Author(s):  
E. Harju ◽  
R. Punnonen ◽  
R. Tuimala ◽  
J. Salmi ◽  
I. Paronen
Keyword(s):  
Vitamin D ◽  
Parathyroid Hormone ◽  
Serum Levels ◽  
Serum Calcitonin ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
Age Related ◽  
Neck Fracture ◽  
25 Hydroxyvitamin D

The effects on general and bone metabolism of femoral neck fracture patients of 0.25 μg α-calcoid given orally twice daily ( n=9) and 25 μg calcitonin given subcutaneously 30 times ( n=10) in 10 weeks were studied against a control ( n=ll). Bone histology and histomorphometry showed non-age related osteoporosis in 30% and osteomalacia in 22% of the patients studied. Impaired serum vitamin D status was found in 47 – 88% of patients, secondary hyperparathyroidism and increased serum parathyroid hormone in 59% and decreased serum calcitonin levels in 69%. On histology, normal findings and non-age related osteoporosis on histology were associated with low serum levels of 25-hydroxyvitamin D3,1,25- and 24,25-dihydroxy vitamin D3. Very high serum levels of 1,25-dihydroxyvitamin D3 and low levels of 25-hydroxyvitamin D3 occurred in fracture patients with osteomalacia. Calcitonin improved calcium balance, reduced osteoporosis and increased the serum 1,25- and 24,25-dihydroxyvitamin D3 levels but had no effect on osteomalacia. Vitamin D reduced osteomalacia, slightly increased the serum 1,25-dihydroxyvitamin D3 concentration and decreased serum levels of parathyroid hormone. Both treatments gave a similar slight decrease in serum calcitonin concentrations. A mechanism of action for the treatments is suggested.

Metabolism of 25-hydroxyvitamin D in copper-laden rat: a model of Wilson's disease

1988 ◽  
Vol 254 (2) ◽  
pp. E150-E154
Author(s):  
T. O. Carpenter ◽  
M. L. Pendrak ◽  
C. S. Anast
Keyword(s):  
Vitamin D ◽  
Wilson’S Disease ◽  
Wilson's Disease ◽  
Vitamin D Metabolism ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
Hepatic Copper ◽  
25 Hydroxyvitamin D ◽  
Potential Factor

Wilson's disease results in excess tissue accumulation of copper and is often complicated by skeletal and mineral abnormalities. We investigated vitamin D metabolism in rats fed a copper-laden diet rendering hepatic copper content comparable with that found in Wilson's disease. Injection of 25-hydroxyvitamin D3 [25(OH)D3] resulted in reduced 1,25-dihydroxyvitamin D [1,25(OH)2D] levels in copper-intoxicated rats. In vitro 25(OH)D-1 alpha-hydroxylase activity was impaired in renal mitochondria from copper-intoxicated animals. Activity was also inhibited in mitochondria from controls when copper was added to incubation media. Impaired conversion of 25(OH)D to 1,25(OH)2D occurs in copper intoxication and suggests that altered vitamin D metabolism is a potential factor in the development of bone and mineral abnormalities in Wilson's disease.

scholarly journals Association of Differing Qatari Genotypes with Vitamin D Metabolites

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Youssra Dakroury ◽  
Alexandra E. Butler ◽  
Soha R. Dargham ◽  
Aishah Latif ◽  
Amal Robay ◽  
...  
Keyword(s):  
Vitamin D ◽  
Skin Pigmentation ◽  
Genetic Differences ◽  
Vitamin D Metabolites ◽  
Vitamin D Metabolism ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
Increased Risk ◽  
25 Hydroxyvitamin D

Objective. Genetic studies have identified four Qatari genotypes: Q1 Arab, Bedouin; Q2 Asian/Persian; Q3 African; and a fourth admixed group not fitting into the previous 3 groups. This study was undertaken to determine if there was an increased risk of deficiency of vitamin D and its metabolites associated with differing genotypes, perhaps due to genetic differences in skin pigmentation. Methods. 398 Qatari subjects (220 type 2 diabetes and 178 controls) had their genotype determined by Affymetrix 500 k SNP arrays. Total values of 1,25-dihydroxyvitamin D (1,25(OH)2D), 25-hydroxyvitamin D (25(OH)D), 24,25-dihydroxyvitamin D (24,25(OH)2D), and 25-hydroxy-3epi-vitamin D (3epi-25(OH)D) concentrations were measured by the LC-MS/MS analysis. Results. The distribution was as follows: 164 (41.2%) genotyped Q1, 149 (37.4%) genotyped Q2, 31 (7.8%) genotyped Q3, and 54 (13.6%) genotyped “admixed.” Median levels of 25(OH)D and 3epi-25(OH)D did not differ across Q1, Q2, Q3, and “admixed” genotypes, respectively. 1,25(OH)2D levels were lower (p<0.04) between Q2 and the admixed groups, and 24,25(OH)2D levels were lower (p<0.05) between Q1 and the admixed groups. Vitamin D metabolite levels were lower in females for 25(OH)D, 1,25(OH)2D (p<0.001), and 24,25(OH)2D (p<0.006), but 3epi-25(OH)D did not differ (p<0.26). Diabetes prevalence was not different between genotypes. Total 1,25(OH)2D (p<0.001), total 24,25(OH)2D (p<0.001), and total 3epi-25(OH)D (p<0.005) were all significantly lower in diabetes patients compared to controls whilst the total 25(OH)D was higher in diabetes than controls (p<0.001). Conclusion. Whilst 25(OH)D levels did not differ between genotype groups, 1,25(OH)2D and 24,25(OH)2D were lower in the admixed group, suggesting that there are genetic differences in vitamin D metabolism that may be of importance in a population that may allow a more targeted approach to vitamin D replacement. This may be of specific importance in vitamin D replacement strategies with the Q2 genotype requiring less, and the other genotypes requiring more to increase 1,25(OH)2D. Whilst overall the group was vitamin D deficient, total 25(OH)D was higher in diabetes, but 1,25(OH)2D, 24,25(OH)2D, and 3epi-25(OH)D were lower in diabetes that did not affect the relationship to genotype.

scholarly journals Reshaping the way we view vitamin D signalling and the role of vitamin D in health

2004 ◽  
Vol 17 (2) ◽  
pp. 241-248 ◽  
Author(s):  
James C. Fleet ◽  
Jie Hong ◽  
Zhentao Zhang
Keyword(s):  
Vitamin D ◽  
Transcriptional Activation ◽  
Mode Of Action ◽  
Uv Light ◽  
Active Form ◽  
Vitamin D Metabolism ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
25 Hydroxyvitamin D ◽  
Molecular Mode

AbstractAlthough the biological requirement for vitamin D can be met by epidermal exposure to UV light, there are a number of conditions where this production does not occur or is not sufficient to meet biological needs. When this happens, vitamin D must be consumed and is a nutrient. However, two distinct observations have caused researchers to rethink certain dogma in vitamin D biology. First, it appears that in addition to the hormonally active form of 1,25 dihydroxyvitamin D (1,25(OH)2D), circulating levels of 25 hydroxyvitamin D have a critical importance for optimal human health. This and other data suggest that extra-renal production of 1,25(OH)2D contributes to Ca homeostasis and cancer prevention. Second, in addition to its role in the transcriptional activation of genes through the vitamin D receptor there is now compelling evidence that 1,25(OH)2D has a second molecular mode of action; the rapid activation of second-messenger and kinase pathways. The purpose of this second mode of action is only now being explored. The present review will discuss how these two areas are reshaping our understanding of vitamin D metabolism and action.

Vitamin D3 metabolism in a pig strain with pseudo vitamin D-deficiency rickets, type I

1987 ◽  
Vol 115 (3) ◽  
pp. 345-352 ◽  
Author(s):  
Reinhard Kaune ◽  
Johein Harmeyer
Keyword(s):  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Type I ◽  
Vitamin D Metabolism ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
Before And After ◽  
25 Hydroxyvitamin D ◽  
Deficiency Rickets ◽  
Clinical Healing

Abstract. Vitamin D metabolism was studied in the 'Hannover Pig', a strain which suffers from pseudo vitamin D-deficiency rickets, type I. Animals of this strain are known to be devoid of renal 25-hydroxyvitamin D3-1α-hydroxylase and -24-hydroxylase activities. Pigs with florid rickets and hypocalcaemia were treated with single im injections of 0.25 to 1.25 mg of vitamin D3, doses that have been shown in previous studies to be effective in producing transient healing of rachitic symptoms. The levels of vitamin D3 and its most relevant physiological metabolites in plasma were estimated at intervals before and after this vitamin D3 treatment. Vitamin D3 rose from 14.8 ± 8.1 to 364 ± 190 nmol/l (mean ± sd) 2 to 3 days post injectionem, 25-hydroxyvitamin D3 from 131.0 ± 46.2 to 1068 ± 160 nmol/l within 7 days post injectionem. The 1α,25-dihydroxyvitamin D3 concentration in plasma was elevated from 73.9 ± 25.0 to 281 ± 168 pmol/l 2 to 3 days post injectionem and declined continually from that time. 24R,25-dihydroxyvitamin D3 and 25S,26-dihydroxyvitamin D3 levels after treatment showed different responses in different animals being either elevated or unchanged. Clinical healing of the pigs with these doses of vitamin D3 was attributed to the transient rise of 1α,25-dihydroxyvitamin D3 in plasma. It was assumed that 1α,25-dihydroxyvitamin D3 synthesis takes place under these circumstances in extrarenal tissues.

scholarly journals IGF-I and GH stimulate Phex mRNA expression in lungs and bones and 1,25-dihydroxyvitamin D(3) production in hypophysectomized rats

2002 ◽  
pp. 97-105 ◽  
Author(s):  
E Zoidis ◽  
M Gosteli-Peter ◽  
C Ghirlanda-Keller ◽  
L Meinel ◽  
J Zapf ◽  
...  
Keyword(s):  
Vitamin D ◽  
Mrna Expression ◽  
Type I ◽  
Serum Osteocalcin ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
Igf I ◽  
Hypophysectomized Rats ◽  
25 Hydroxyvitamin D

OBJECTIVE: X-linked hypophosphatemia, a renal phosphate (Pi)-wasting disorder with defective bone mineralization, is caused by mutations in the PHEX gene (a Pi-regulating gene with homology to endopeptidases on the X chromosome). We wondered whether changes in Phex and neprilysin (NEP) (another member of the family of zinc endopeptidases) mRNA expression could be observed in relation to vitamin D and Pi metabolism during GH- and IGF-I-stimulated growth of hypophysectomized rats. DESIGN: Animals were infused s.c. for 2 days with vehicle, 200 mU (67 microg) GH or 300 microg IGF-I/rat per 24 h. We determined serum osteocalcin and osteocalcin mRNA in bone, Phex mRNA in bone and lungs, serum 1,25-dihydroxyvitamin D(3) (1,25-(OH)(2)D(3)) and serum Pi levels, and renal expression of 25-hydroxyvitamin D(3)-1alpha-hydroxylase (1alpha-hydroxylase), of 25-hydroxyvitamin D(3)-24-hydroxylase (24-hydroxylase) and of the Na-dependent Pi-cotransporter type I and II (Na(d)Pi-I and -II). RESULTS: As compared with vehicle-treated controls, body weight and tibial epiphyseal width significantly increased in GH- and IGF-I-treated animals. Serum osteocalcin and osteocalcin mRNA levels in bone, Phex mRNA in bone and lungs, serum 1,25-(OH)(2)D(3) and renal 1alpha-hydroxylase mRNA rose concomitantly, whereas expression of NEP in lungs was barely affected and renal 24-hydroxylase mRNA decreased. Na(d)Pi-I and -II gene expression in the kidney and serum Pi levels remained unchanged. CONCLUSIONS: Our findings suggest a coordinate regulation of Phex mRNA expression in lungs and bone and vitamin D metabolism during GH- and IGF-I-stimulated growth.

Effects of streptozotocin-induced diabetes on circulating levels of vitamin D metabolites

1983 ◽  
Vol 104 (1) ◽  
pp. 96-102 ◽  
Author(s):  
Hitoshi Ishida ◽  
Yutaka Seino ◽  
Kinsuke Tsuda ◽  
Jiro Takemura ◽  
Sigeo Nishi ◽  
...  
Keyword(s):  
Vitamin D ◽  
Diabetic Rats ◽  
Plasma Vitamin ◽  
Vitamin D Metabolites ◽  
Vitamin D Metabolism ◽  
Plasma Urea ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
Streptozotocin Induced Diabetes ◽  
25 Hydroxyvitamin D

Abstract. In order to investigate vitamin D metabolism in insulin-deficient diabetic rats, plasma vitamin D metabolites were measured at various periods after induction of diabetes by iv administration of 60 mg/kg streptozotocin (STZ). After STZ injection, plasma insulin was significantly decreased and plasma urea nitrogen increased with the duration of diabetes, while plasma creatinine remained unchanged. Plasma calcium, 25-hydroxyvitamin D (25(OH)D), and 24,25-dihydroxyvitamin D (24,25(OH)2D) progressively decreased. On the other hand, plasma 1,25-dihydroxyvitamin D (1,25(OH)2D) did not change at any period, but the ratio of 1,25(OH)2D to 25(OH)D became high in proportion to the severity of hypocalcaemia. Since significantly lower 25(OH)D and 24,25(OH)2D levels were observed at the later stage of diabetes, it is suggested that the altered vitamin D metabolism in diabetes is secondary to the disturbances in metabolic homeostasis derived form the insulin deficiency.

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